Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis.
Journal: JAMA neurology
Volume: 80
Issue: 7
Year of Publication: 2023
Affiliated Institutions:
Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
University of Ottawa, Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Department of Medical Sciences, Neurology, Uppsala University, Uppsala, Sweden.
Department of Neurology, St Vincent's Hospital Sydney, Sydney, New South Wales, Australia.
St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
Department of Neurology, Austin Health, Melbourne, Victoria, Australia.
University of Melbourne, Melbourne, Victoria, Australia.
Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Department of Haematology, Haukeland University Hospital, Bergen, Norway.
Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
Department of Haematology, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
Department of Haematology, rd Faculty of Medicine, Charles University in Prague, and University Hospital Kralovske Vinohrady, Prague, Czech Republic.
Department of Neurology, The Alfred Hospital, Melbourne, Victoria, Australia.
University of Queensland, Brisbane, Queensland, Australia.
School of Medicine and Public Health, University Newcastle, Newcastle, New South Wales, Australia.
Department of Neurology, Antwerp University Hospital, Edegem, Belgium.
UOC Neurologia, Azienda Sanitaria Unica Regionale Marche-AV, Macerata, Italy.
Dokuz Eylul University, Konak, Izmir, Turkey.
Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait.
Neurologic Clinic and Policlinic, Departments of Medicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania, Italy.
CHUM MS Center and Universite de Montreal, Montreal, Quebec, Canada.
IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon.
Flinders University, Adelaide, South Australia, Australia.
Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.
Liverpool Hospital, Sydney, New South Wales, Australia.
Monash Medical Centre, Melbourne, Victoria, Australia.
Garibaldi Hospital, Catania, Italy.
Department of Neurology, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal.
Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Academic MS Center Zuyderland, Department of Neurology, Zuyderland Medical Center, Sittard-Geleen, the Netherlands.
Department of Neurology, University Hospital Ghent, Ghent, Belgium.
Department of Neurology, Hacettepe University Hospitals, Ankara, Turkey.
Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy.
Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Department of Neurology, Razi University Hospital, Manouba, Tunis, Tunisia.
Hospital Universitario Donostia, San Sebastián, Spain.
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
Department of Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.
Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.
Westmead Hospital, Sydney, New South Wales, Australia.
Hospital de Galdakao-Usansolo, Galdakao, Spain.
University Hospital Reina Sofia, Cordoba, Spain.
Center of Neuroimmunology, Service of Neurology, Hospital Clinic de Barcelona, Barcelona, Spain.
Department of Medicine, Sultan Qaboos University Hospital, Al-Khodh, Oman.
Department of Neurology, Buffalo General Medical Center, Buffalo, New York.
Universidade Metropolitana de Santos, Santos, Brazil.
Groene Hart Ziekenhuis, Gouda, the Netherlands.
Perron Institute, University of Western Australia, Nedlands, Western Australia, Australia.
Abstract summary
Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS).To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials.This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics.AHSCT vs fingolimod, natalizumab, or ocrelizumab.Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement.Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%).In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time.
Authors & Co-authors:
Kalincik Tomas T
Sharmin Sifat S
Roos Izanne I
Freedman Mark S MS
Atkins Harold H
Burman Joachim J
Massey Jennifer J
Sutton Ian I
Withers Barbara B
Macdonell Richard R
Grigg Andrew A
Torkildsen Øivind Ø
Bo Lars L
Lehmann Anne Kristine AK
Havrdova Eva Kubala EK
Krasulova Eva E
Trnený Marek M
Kozak Tomas T
van der Walt Anneke A
Butzkueven Helmut H
McCombe Pamela P
Skibina Olga O
Lechner-Scott Jeannette J
Willekens Barbara B
Cartechini Elisabetta E
Ozakbas Serkan S
Alroughani Raed R
Kuhle Jens J
Patti Francesco F
Duquette Pierre P
Lugaresi Alessandra A
Khoury Samia J SJ
Slee Mark M
Turkoglu Recai R
Hodgkinson Suzanne S
John Nevin N
Maimone Davide D
Sa Maria Jose MJ
van Pesch Vincent V
Gerlach Oliver O
Laureys Guy G
Van Hijfte Liesbeth L
Karabudak Rana R
Spitaleri Daniele D
Csepany Tunde T
Gouider Riadh R
Castillo-Triviño Tamara T
Taylor Bruce B
Sharrack Basil B
Snowden John A JA
Mrabet Saloua S
Garber Justin J
Sanchez-Menoyo Jose Luis JL
Aguera-Morales Eduardo E
Blanco Yolanda Y
Al-Asmi Abdullah A
Weinstock-Guttman Bianca B
Fragoso Yara Y
de Gans Koen K
Kermode Allan A
Study Outcome
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